Tissue Perfusion and Biomarkers Assessment Following Root Coverage Procedures

AIM To assess tissue perfusion changes and wound healing biomarker levels after root coverage procedures with coronally advanced flap in combination with the cross-linked xenogeneic collagen matrix (CCMX), loaded either with a placebo or recombinant human platelet-derived growth factor-BB (rhPDGF). METHODS This study was designed as a secondary analysis from a previously published clinical trial, and it assessed the tissue perfusion changes over 6 months around multiple gingival recession defects, treated with either with CCMX alone (control) or with CCMX + rhPDGF (test). High frequency Doppler ultrasonography (HFUS) scans were obtained at sites of interest at baseline, 2 weeks, 3 months, and 6 months after surgery. Dynamic tissue perfusion measurements (DTPMs) were performed at the midfacial, interproximal, and transverse aspects of the teeth by an operator, blinded to treatment allocation, using a software package. The expression of different wound healing biomarkers from the gingival crevicular fluid was also assessed. RESULTS The regression analyses showed similar tissue perfusion changes between the two groups throughout the majority of the 6 months. DTPMs at 2 weeks showed the test group to have significantly higher perfusion relief intensity (pRI, p < 0.001), mean perfused area (pA, p < 0.001), mean blood flow intensity (FI$_{mean}$, p = 0.021), and total blood flow intensity (FI$_{tot}$, p = 0.021) at the graft region of interest (ROI) compared to control sites. The test sites also exhibited significantly greater pA (p = 0.033) and blood flow intensity "blue" (FI$_{blue}$, meaning flow away from the transducer, p = 0.035) at the level of the flap compared to the control sites. At 2 weeks, FI$_{blue}$ of the graft was directly correlated with the final mean root coverage (p = 0.008) and complete root coverage (p = 0.003). FI$_{mean}$ and FI$_{tot}$ of the graft exhibited a direct correlation with volume gain at 6 months (p = 0.031 for both parameters). The final GT gain was correlated to the early DTPMs (pA and FI$_{blue}$) of the graft and the flap. The two groups exhibited different expressions of IL-1β, PDFG-BB, and VEGF over 3 months, with the 1-week levels of PDGF-BB that were associated with time to recovery. CONCLUSIONS HFUS allowed exquisite assessment of tissue perfusion occurring at the entire surgical reconstructive regions and also within the flap and the graft. Sites treated with CCMX + rhPDGF exhibited higher DTPMs, primarily within the graft and flap ROIs at the 2-week timepoint compared to sites augmented with CCMX + saline. Early DTPMs at the graft and flap ROIs showed associations with PROMs and the final clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov: NCT04462237.